I Love Me Some High-Dose NTG and NIV for SCAPE

Background: Hypertensive acute heart failure is a subgroup of acute congestive heart failure (CHF) patients.  Physiologically there is increased afterload and decreased venous capacitance both leading to fluid shifts resulting in pulmonary vascular congestion.  Sympathetic crashing acute pulmonary edema (SCAPE) is a severe form of hypertensive acute CHF.  The rapidity and severity of this illness leaves a very narrow period of time for therapeutic intervention before subsequent deterioration. Therapeutic intervention includes vasodilators such as, high-dose nitroglycerin (NTG) and non-invasive ventilation (NIV). Both therapies can result in reduced work of breathing, decreased preload/afterload, and prevention of endotracheal intubation, and ventilation.  There is a paucity of high level literature on this topic. However, many resuscitation-minded clinicians advocate for this therapy.

Paper: Mathew R et al. High-Dose Nitroglycerin Bolus for Sympathetic Crashing Acute Pulmonary Edema: A Prospective Observational Pilot Study. JEM 2021. PMID: 34215472 [Access on Read By QxMD]

 Clinical Question: What is the safety and feasibility of high-dose nitroglycerin combined with non-invasive ventilation (NIV) in sympathetic crashing acute pulmonary edema (SCAPE)?

What They Did:

  • Prospective, observational pilot study done in a single tertiary care ED
  • All patients were treated with high-dose NTG and NIV (Protocol Below)


  • Primary: Feasibility and safety of high-dose NTG combined with NIV in SCAPE
    • Resolution of symptoms in 6hrs
      • Defined as:
        • Decrease in RR by 25% of initial reading
        • RR≤24 BPM with patient maintaining saturations >90% on RA or ≥95% on supplemental oxygen
        • Subjective improvement in dyspnea and use of accessory muscles
        • SBP of <160mmHg
        • Disappearance of course crepitations in all lung fields (or disappearance of B-line on lung US)
      • Need for intubation
      • Any complications associated with high-dose NTG
    • Secondary:
      • Mean bolus of NTG given
      • Infusion/hr doses of NTG given 


  • Consecutive patients aged >18 years who presented with hypertensive acute CHF
  • SCAPE = Acute onset respiratory distress of <6hrs, with a respiratory rate of >30BPM, bilateral coarse crepitations, and oxygen saturation of <90% on RA or <95% on oxygen associated with sympathetic surge (i.e. diaphoresis, tachycardia, and agitation), and BP >160/100mmHg 


  • Required immediate intubation or cardiopulmonary resuscitation
  • Contraindication to NTG (i.e. allergic to NTG, aortic stenosis, HOCM, using sildenafil within 24hrs or tadalafil within 48hrs)
  • Acute coronary syndrome


  • Recruited 25 patients
    • Mean age = 44.2 years
    • Mean duration of symptoms = 3.2hrs
  • NTG Results:
    • Mean bolus dose of NTG given = 872ug
    • Mean cumulative dose of NTG given = 35mg
    • No incidence of hypotension after the bolus dose of nitroglycerin
    • 2/25 patients had transient hypotension during infusion of NTG that improved with small fluid bolus and d/c of NTG drip
  • NIV Results:
    • 6/25 patients with maximum inspiratory positive airway pressure = 16cmH20
    • 12/25 patients required low dose opioids (fentanyl 50ug) to improve mask tolerability
  • Clinical Outcomes:
    • 11/25 patients had resolution of symptoms at 3hrs
      • Remaining 13/25 patients had symptom resolution within 6hrs
    • 24/25 patients were discharged from the ED after a brief period of observation
      • Average LOS for patients discharged home was 15hrs
    • 1/25 patients did not tolerate mask and required intubation within 6hrs 


  • Asks a clinically important question in an area with a paucity of high-level evidence
  • Establishes a pragmatic, objective, feasible protocol that can be used in patients with SCAPE at most EDs


  • Single-center pilot study with a small sample size
  • Only assessed outcomes up to 6 to 15hrs. A lack of longer term follow up precludes recognition of recurrent symptoms, subsequent decompensation, and/or any prolonged effects of NTG
  • No comparison to a standard care arm
  • Observational trial only allows for associations of effect not causation of effect


  • An important point to understand is most patients with SCAPE are euvolemic, where diuresis will have little role. This is why the use of high dose NTG and NIV make more physiologic sense in the acute treatment of this disease [2][3][4]
  • The biggest challenge in the use of NIV, will be patient tolerability. Use of low dose opioids (i..e morphine 2mg or fentanyl 50ug) may help with this as was seen in this observational trial

Author Conclusion: “Use of our specific SCAPE treatment algorithm, which included high-dose NTG and NIV, was safe and provided rapid resolution of symptoms.” 

Clinical Take Home Point: In patients presenting with SCAPE the use of high dose NTG (600 – 1000mcg) bolus + NTG drip (100ug/min) + NIV is a safe, objective practice to help reduce the incidence of intubation and ICU admission.


  1. Mathew R et al. High-Dose Nitroglycerin Bolus for Sympathetic Crashing Acute Pulmonary Edema: A Prospective Observational Pilot Study. JEM 2021. PMID: 34215472 [Access on Read By QxMD]
  2. Zile MR et al. Transition from Chronic Compensated to Acute Decompensated Heart Failure: Pathophysiological Insights Obtained from Continuous Monitoring of Intracardiac Pressures. Circ 2008. PMID: 18794390
  3. Chaudhry SI et al. Patterns of Weight Change Preceding Hospitalization for Heart Failure. Circ 2007. PMID: 17846286
  4. Fallick C et al. Sympathetically Mediated Changes in Capacitance: Redistribution of the Venous Reservoir as a Cause of Decompensation. Circ Heart Fail 2011. PMID: 21934091
  5. Wilson SS et al. Use of Nitroglycerin by Bolus Prevents Intensive Care Unit Admission in Patients with Acute Hypertensive Heart Failure. AJEM 2017. PMID: 27825693

For More Thoughts on This Topic Checkout:

Post Peer Reviewed By: Anand Swaminathan, MD (Twitter: @EMSwami)

Cite this article as: Salim Rezaie, "I Love Me Some High-Dose NTG and NIV for SCAPE", REBEL EM blog, July 12, 2021. Available at: https://rebelem.com/i-love-me-some-high-dose-ntg-and-niv-for-scape/.

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